tbuckley/cabot-search huggingface dataset:
Abstract 13145: Mixed Digital Model of Care in Real-Time for Mexican Patients With Heart Failure
Authors: CARLOS GUIZAR, Amada Alvarez, ANTONIO JORDAN, Arturo Mendez, JUAN CARLOS DE LA FUENTE MANCERA, FRANCISCO BARANDA, DANYA RODRIGUEZ, ARANTXA VELAZQUEZ, Rafael Cacelin, NANCY LOPEZ, LUIS DALI, THANIA ZURITA, ULISES GOMEZ ALVAREZ, Maria del Refugio Aguilar Serrano, SONIA JUAREZ, ARELI RODRIGUEZ, Juan Collado, LUIS TEJADO
Journal: Circulation (2022)

Introduction Decompensated heart failure (DHF) is the main cause of cardiovascular hospitalization. During 1-year follow-up (FU), at least one rehospitalization occurred in 56.6% of patients with HF. In Mexico, HF places great burden on patients, caregivers, and healthcare systems. New strategies are essential for early diagnosis and treatment of DHF. Hypothesis: Use of a digital tool is effective for remote monitoring of patients with CHF to reduce the number of hospitalizations and/or unscheduled visits to the ER. Methods: A mixed digital model of HF (MDM-HF) care has been developed. It included an app in patient’s mobiles (CardioEnlace) that allowed real time monitoring of key parameters. These data were transferred into HF Unit portal and integrated into the patient's clinical file. CardioEnlace allowed detection of decompensation events through 1) alerts by patient′s text messages and 2) system alerts when variables were out of security limits on three or more consecutive days. If a patient showed signs of DHF, he/she was reached to provide medical instructions and/or scheduled an early appointment. Results: MDM-HF care was deployed in July 2021. Up to date 131 patients have been included. The median of age is 58 years (interquartile range 47.5-65.5) and 77.1% were male. Cardiovascular risk factors (CVRF) frequencies are shown in Table 1. HF was secondary to ischemic condition in 44.5% of the patients. At least one hospitalization in the previous 2 years was reported in 73.5% of the subjects. Cardio Enlace parameters are shown in Fig 1. A blood pressure &lt;140/90 mmHg was reported in 89.5% of patients and the average exercise time was 32 min/day. CardioEnlace alerts from January 2022 to date, were 82. Reasons are shown in Table 2. Adjustments to the treatment were done immediately and none of the patients had been hospitalized. Discussion: MDM-HF care model supports an early detection of DHF and monitorization of CVRF treatment which affect around 50% of the patients. Follow-up evaluations would allow to assess its impact on hospitalizations/emergency admissions. MDM-HF care model is part of the HF National Mexican Registry that will integrate data-driven solutions to reduce lead times from diagnosis to therapy adjustments and reduce the economic burden of DHF.
Abstract 13724: Development of VS-041 as a Precision Medicine Targeting Cardiac-Relevant Matrix Metalloproteases (MMPs) in Heart Failure With Preserved Ejection Fraction (HFpEF)
Authors: Artur Plonowski, Benjamin Pratt, Magdalena Krupa, Piotr Lipinski, Mark Herbert
Journal: Circulation (2022)

Introduction. HFpEF is a heterogeneous syndrome, with several underlying etiologic and pathophysiologic factors. As “one size fits all” therapies are not equally efficacious across various HFpEF comorbidities, a precision medicine approach can offer a disease modifying treatment for HFpEF subpopulation stratified for specific molecular targets. Expression of MMP2, 9, and 13 in heart is elevated in HFpEF patients with hypertension, diabetes or coronary disease, and their levels in plasma correlate with survival, suggesting utility as predictive biomarkers. Genetic ablation of MMP2, 9, and 13 leads to a robust antifibrotic effect in the myocardium. Inhibition of MMP2, 9, and 13 directly regulates of Ca 2+ transients and protects sarcomere function. Hypothesis. We present preclinical profile of VS-041, a novel and narrow-spectrum MMP inhibitor, as a drug candidate for HFpEF patients with elevated levels of MMP2, 9, and 13. Methods and Results. VS-041, optimized with computer-aided drug design methods, shows single-digit IC 50 against MMP2 (1nM), MMP9 (2nM) and MMP13 (1nM), and maintains &gt;300-fold selectivity against MMP1 and TACE. In isolated cardiomyocytes VS-041 reduces contractility deficit due to fast pacing. With high predicted metabolic bioavailability (MF%=90), &gt;80% target occupancy by VS-041 is estimated after 50 mg/kg PO dose in rats. VS-041 demonstrated robust efficacy in Dahl Salt Sensitive rat model of hypertension and HFpEF after dosing at 25 or 50 mg/kg PO for 5 wks in a therapeutic mode (after 1-wk of high salt lead-in). VS-041 had no effect on blood pressure or ejection fraction confirming a direct effect on diastolic function. In Doppler mitral inflow, analysis of the isovolumic relaxation time and the E/A ratio of peak velocity of filling waves revealed 40% improvement in diastolic function. LV fibrosis was dose-proportionally decreased based on PSR morphometry. No adverse effects were observed after 5 weeks of dosing. Conclusions. Preclinical pharmacology and safety profile of VS-041 support its nomination as clinical candidate and initiation of IND-enabling studies. VS-041 has potential to be first-in-class precision medicine treatment for HFPEF patients with elevated levels of cardiac-relevant MMP2, 9 and 13.
Abstract 11480: Telmisartan to Improve Walking Performance in People With Lower Extremity Peripheral Artery Disease: The Telex Randomized Clinical Trial
Authors: Mary M McDermott, Lydia Bazzano, Charlotte A Peterson, Robert Sufit, Luigi Ferrucci, Lihui Zhao, Tamar S Polonsky, Dongxue Zhang, Kathryn Domanchuk, Donald Lloyd-Jones, Christiaan Leeuwenburgh, Jack Guralnik, Melina R Kibbe, Kate Kosmac, Michael H Criqui, Lu Tian
Journal: Circulation (2022)

BACKGROUND. People with lower extremity peripheral artery disease (PAD) have reduced lower extremity perfusion, impaired lower extremity skeletal muscle function, and poor walking performance. Telmisartan, an angiotensin receptor blocker (ARB), has properties that reverse these abnormalities. This randomized clinical trial tested whether telmisartan improved six-minute walk distance, compared to placebo, in people with PAD at 6-month follow-up. METHODS. This multi-centered randomized clinical trial was designed as a 2 x 2 factorial design, comparing the effects of telmisartan plus supervised exercise therapy (SET) to telmisartan alone and SET alone, respectively and comparing telmisartan alone to placebo. PAD participants were randomized to one of four groups: telmisartan+SET (N=30), telmisartan + attention control (N=29), placebo + SET (N=28), or placebo+ attention control (N=27) for six months. Due to slower than anticipated enrollment, the primary comparison was changed to a comparison of the two telmisartan groups combined to the two placebo groups combined. The primary outcome was 6-month change in 6-minute walk distance. Secondary outcomes were maximal treadmill walking distance, the Walking Impairment Questionnaire distance, speed, and stair climbing scores, and the short-form 36 physical functioning score. Results adjusted for site, baseline six-minute walk distance, randomization to SET vs. attention control, and group differences in the prevalence of sex and heart failure at baseline. RESULTS. Of 114 randomized patients (mean [SD] age, 67.3 [9.9] years, 46 (40.4%) female, 81 (71.1%) Black), 105 (92%) completed 6-month follow-up. See the Table for results. CONCLUSIONS. These results do not support telmisartan for improving objectively measured walking performance or patient reported outcomes in patients with PAD.
Abstract 13954: Cardiovascular Imaging Markers and Atherosclerotic Cardiovascular Disease in Lung Cancer Survivors
Authors: Lili Zhang, Yasmeen M Daraz, Mariana Kawalet, Paul Ippolito, Patrick Neshiwat, Nitin Ohri, Min Pu, Mario J Garcia, Leandro Slipczuk, Carlos Rodriguez
Journal: Circulation (2022)

Introduction: Lung cancer survivors have heightened risk of atherosclerotic cardiovascular disease (ASCVD) due to shared risk factors. Chest computed tomography (CT) is routinely performed for cancer staging and radiotherapy (RT) planning. However, the extent of coronary artery calcium (CAC) and thoracic aortic calcium (TAC) is not routinely evaluated for ASCVD risk assessment. Methods: We evaluated the extent of CAC and TAC from chest CTs obtained for routine care prior to RT in a cohort of lung cancer survivors from 2007 to 2021 at a single academic health system that serves a large multiracial community. The demographics, baseline cardiovascular risk factors and baseline ASCVD (the composite of myocardial infarction, cerebrovascular disease, or peripheral arterial disease) were compared between survivors with and without CAC or TAC. The primary end point was incident ASCVD. Results: The cohort studied 603 subjects, including 19% non-Hispanic Whites, 33% non-Hispanic Blacks and 32% Hispanics. Mean age was 65±11 years, with 45% women. CAC was present in 72% of subjects and TAC in 85%. Individuals with CAC had higher prevalence of hypertension (75% vs 57%, p&lt;0.001), diabetes (41% vs 20%, p&lt;0.001) and hyperlipidemia (49% vs 26%, p&lt;0.001). Survivors with CAC had a higher prevalence of baseline ASCVD (33% vs 18%, p=0.001). Survivors with TAC yielded similar findings. In individuals without prior ASCVD, 10-year ASCVD risk score was higher in survivors with CAC (20%±21% vs 12%±13%, p=0.009) or with TAC (19%±20% vs 8%±8%, p=0.007). In a median follow-up time of 15 months, the new development of ASCVD appeared higher in survivors with CAC (23% vs 14%, p=0.04, Figure A) and with TAC (22% vs 8%, p=0.01, Figure B). Conclusions: In a large cohort of multiracial lung cancer survivors, presence of CAC or TAC based on routine chest CT at baseline is associated with a higher burden of ASCVD risk and predicts a higher risk of the new development of ASCVD during follow- up.
Abstract 14781: Simultaneous Profiling of Genotype and Transcriptome at Single Cell Resolution Identifies Cellular Programs Underlying Clonal Hematopoiesis Pathology
Authors: Brett Heimlich, Pawan Bhat, Alyssa C Parker, Jessica Ulloa, Sydney Olson, P. Brent Ferrell, Alexander G Bick
Journal: Circulation (2022)

Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) results from a clonal expansion of hematopoietic stem cells due to somatic mutations in genes such as DNMT3A or TET2. Patients with CHIP have poor cardiovascular outcomes. TET2 CHIP clones that make up &gt;20% of blood increases risk. Whether CHIP mutated cells confer risk directly or through polarizing other cells is presently unknown as prior work has been unable to simultaneously resolve mutational status and transcriptome of an individual cell. Methods: We performed single cell RNA-seq on blood from patients with DNMT3A CHIP (N=9), TET2 CHIP (N=8), and controls (N=6). We identified individual cell CHIP mutational status with a novel method that leverages mitochondrial mutations to identify cell lineage. Results: Across 104,556 single cells, CHIP patients had a higher proportion of CD14 monocytes (32% vs. 18%). Within individuals, CHIP mutated cells exhibited a strong myeloid bias. At the extreme, 93% of TET2 mutated cells were monocytes in one patient. Comparing TET2 CHIP monocytes to controls identified a hyper-inflammatory phenotype with increased expression of inflammatory cytokines and their downstream targets, and elevated expression of adhesion molecules. Comparing TET2-mutated CD14 monocytes to unmutated monocytes within the same individual localized the inflammatory phenotype to the mutated cells. Conversely, this phenotype was not observed in DNMT3A CHIP monocytes either in aggregate or within the same individual. Conclusions: Simultaneous, high-throughput, single-cell resolution of DNA mutation status and RNA transcriptomes identifies aberrant cellular programs in TET2-mutated CD14 monocytes. Our data support a simple mechanistic model for CHIP cardiovascular disease risk that is proportional to the number of mutated cells present. Differences observed between TET2 and DNMT3A provide a potential explanation for the differential pathogenicity of these two mutations.
Abstract 12920: Mir98 Regulates Myocardial Ischemia-Reperfusion Injury in Late Pregnancy by Targeting Stat3 and Pgc-1α
Authors: Laila Aryan, Lejla Medzikovic, Gregoire Ruffenach, Min Li, Shadie Rahman, Leana Esdin, Ehsan Bastanhagh, Wasila Sun, Mansoureh Eghbali
Journal: Circulation (2022)

INTRODUCTION: We have shown that the late-pregnant (LP) rodent is more vulnerable to myocardial ischemia-reperfusion injury (IRI) compared to non-pregnant (NP). The molecular mechanisms are unknown. Several microRNAs (miRs) are dysregulated in IRI, making them promising therapeutic targets. Our goal is to decipher the mechanisms underlying the higher susceptibility of LP to IRI. Methods: The left anterior descending coronary artery of female Sprague-Dawley rats (2-3 months old NP and LP, 20-21 days pregnant) was occluded for 45 minutes followed by 3 hours reperfusion. Myocardial necrosis was assessed using TTC staining. MicroRNA-microarray profiling was performed on hearts of NP and LP rats subjected to IRI (Ocean Ridge Biosciences). In vitro, female cardiomyocytes were transfected either miR98 mimic or inhibitor (40uM), followed by 3 hours hypoxia and 6 hours reoxygenation. Human blood samples were collected from NP, LP, and coronary heart disease (CHD) patients. Data were expressed as mean±SEM. P&lt;0.05 was considered statistically significant. Results: MicroRNA-microarray profiling revealed miR-98-5p (miR-98) is upregulated in the hearts of LP IRI rats compared to NP IRI by 2.3 folds, which we confirmed with qPCR (1.89±0.15, n=5 animals/group). miR98 is significantly increased in the plasma of healthy LP compared to healthy NP women (2.32±0.44, LP n=9, NP n=7), and significantly increased in LP with CHD compared to healthy LP (4.41±0.73, CHD n=5). TargetScan revealed STAT3 and PGC-1α to be targets of miR98. We confirmed significantly decreased expression of STAT3 and PGC-1α in LP IRI rat myocardium compared to NP IRI (STAT3 0.48±0.12 n=5 and PGC-1α 0.39±0.17 n=5). MiR98 overexpression in female cardiomyocytes subjected to hypoxia/reoxygenation (H/R) significantly decreased STAT3 (0.75±0.11) and PGC-1α (0.52±0.16), and increased apoptosis (1.89±0.09), inflammation (2.12±0.18), and oxidative stress (2.3±0.22), while miR-98 knockdown resulted in the opposite effect (n=4). Conclusions: MiR98 is upregulated in LP rats subjected to IRI compared to NP IRI and in LP human plasma samples with CHD compared to healthy NP and LP. miR98 promotes oxidative stress, inflammation, and apoptosis in the setting of H/R in vitro by targeting STAT3 and PGC-1α.
Abstract 14370: Significant Heterogeneity in Antiplatelet Regimen for Spontaneous Coronary Artery Dissection: A Report of the ISCAD Registry
Authors: Heather L Gornik, Malissa Wood, sahar naderi, Katherine Leon, C M Gibson, Gerald C Chi, Anna Grodzinsky, Bryan Wells, Angela Taylor, Daniella Kadian Dodov, Stanislav Henkin, Samuel Norris, Cassandra Reyes, Fahad Alkhalfan, Clara Vitarello, Esther S Kim
Journal: Circulation (2022)

Introduction: Dual antiplatelet therapy (DAPT) is standard for patients (pts.) with acute coronary syndrome due to atherosclerosis. Evidence to support DAPT vs single antiplatelet therapy (SAPT) for spontaneous coronary artery dissection (SCAD) is limited. Hypothesis: Prescription of DAPT vs SAPT varies among specialized centers for SCAD. Methods: Analysis of 505 pts. with complete patient questionnaire, case report form, and angiography review enrolled in the iSCAD Registry from 9 sites with &gt; 20 pts. enrolled. Data are presented for 442 pts. with complete medication data who received DAPT or SAPT during index hospitalization (HOSP) and continued at discharge (DC). Results: Patient age 49.6 + 10.2 years, 83% were female. Presentation of SCAD: NSTEMI (55.9%), STEMI (26.9%), unstable angina (13.8%), cardiac arrest (4.3%), cardiogenic shock (0.2%). Most common SCAD location was the LAD (60.9%); 20.8% had multivessel SCAD. Management was: medical therapy (75.2%), PCI (22.5%), CABG (1.4%), or PCI + CABG (0.92%). During HOSP 70.1% (317/452) were treated with DAPT vs 29.9% SAPT (135/452). At DC, 74.7% were prescribed DAPT (339/442) vs 25.3% SAPT (112/452). In multivariable analyses, only PCI as SCAD treatment was associated with DAPT during HOSP (OR 3.57, 95% CI 1.90-6.70) or DC (OR 4.9, 95% CI 2.28-10.53). There was significant heterogeneity of antiplatelet regimen across sites ranging from 34.0%-87% DAPT during HOSP (p&lt;0.0001) and 53.8%-83.6% DAPT at DC (p=0.0011) (Figure). There was a trend of recurrent MI among pts. treated with DAPT vs SAPT during HOSP that did not achieve statistical significance (7.1% vs 3.0%, P=0.09). Conclusion: In the iSCAD Registry, most pts. with SCAD were treated with DAPT during index HOSP and DC with significant heterogeneity across sites. PCI during index HOSP was associated with DAPT (vs SAPT) prescription. Further study of outcomes, including recurrent MI, with DAPT (vs SAPT) during hospitalization and subsequent follow-up is needed.
Abstract 12910: Exercise-Induced Specialized Proresolving Mediators Stimulate AMPK Phosphorylation to Promote Mitochondrial Respiration in Macrophages
Authors: Ernesto H Pena Calderin, Jing-Juan Zheng, Nolan Boyd, Lindsey A McNally, Pawel Lorkiewicz, Bradford G Hill, Jason Hellmann
Journal: Circulation (2022)

Emerging epidemiological data suggests that exercise imparts its CVD risk-reducing effects in part through improvements in systemic inflammation. The mechanisms underpinning the salutary effects of physical activity, however, remain incompletely understood. We recently reported that exercise enhances the production of specialized proresolving mediators (SPMs), which act as agonist of inflammation resolution through actions on macrophages (Mϕ). In this study, we find that wheel running accelerated the metabolism of proinflammatory lipid mediators LTB 4 and PGD 2 into their respective metabolites 20-OH-LTB 4 (Sed 27.14±5.88 vs Exe 70.40±10.82 pg/mL; P&lt;0.05; n =3-4) and PGJ 2 (Sed 92.63±16.08 vs Exe 227.90±30.23 pg/mL; P&lt;0.05; n =3-4), resulting in an increase in the ratio of proresolving-to-proinflammatory lipid mediator levels (RvE1+RvD1:leukotrienes; Sed 0.19±0.02 vs Exe 0.32±0.90; P&lt;0.05; n =3-4). These findings were associated with enhanced mitochondrial metabolism in Mϕ, as evidenced by increased basal (Sed 0.12±0.06 vs Exe 1.53±0.07; P&lt;0.05; n =3-4), maximum (Sed 9.20±0.30 vs Exe 12.02±0.82; P&lt;0.05; n =3-4), and ATP-linked oxygen consumption rate (Sed 1.25±0.06 vs Exe 1.47±0.09 pmol/min/μg protein; P&lt;0.05; n =3-4). We also find that SPMs RvD1, RvD2, RvE1 or MaR1 stimulate basal (Ctrl 6.11±0.1 vs RvD1 7.76±0.6 vs RvD2 9.48±0.9 vs RvE1 7.20±0.5 vs MaR1 8.73±0.9 pmol/min/μg protein; P&lt;0.05; n =3) and ATP-linked respiration (Ctrl 2.83±0.2 vs RvD1 4.50±0.3 vs RvD2 4.39±0.2 vs RvE1 4.71±0.3 vs MaR1 4.20±0.2 pmol/min/μg protein; P&lt;0.05; n =3). We find that an increase in basal (Ctrl 1.80±0.13 vs RvD1 2.43±0.19 pmol/min/μg protein; P&lt;0.05; n =3-5) and ATP-linked respiration (Ctrl 1.44±0.10 vs RvD1 1.70±0.15 pmol/min/μg protein; P&lt;0.05; n =3-5) with RvD1 treatment occurs concomitantly with AMPK phosphorylation (Ctrl 1.00±0.07 vs RvD1 1.40±0.02 pAMPK/AMPK fold change; P&lt;0.05; n =3) and inhibiting the kinase activity of AMPK with Compound C abrogates SPM-induced mitochondrial respiration. Taken together, these data suggest that exercise-enhanced SPM production stimulates mitochondrial metabolism in Mϕ via AMPK, which may contribute to exercise-induced amelioration of chronic inflammation.
Abstract 12945: Disparities in the Prevalence of Acute Myocardial Infarction Among Patients With Non-Alcoholic Fatty Liver Disease a Nationwide Database Analysis
Authors: CYRUS M MUNGUTI, Umar Hayat, Hayrettin Okut, Samuel Akidiva, Abdullah Abukar, Wassim H Shaheen
Journal: Circulation (2022)

Background: Non-alcoholic liver disease (NAFLD) is among leading causes of chronic liver disease. Recent evidence suggests an association of NAFLD with cardiovascular diseases; however, few studies have analyzed national level database for this relationships. We aimed to assess the trends and predictors of acute myocardial infarction (AMI) among NAFLD patients in the United States. Methods: The National Inpatient Sample (NIS) database from 2016 to 2019 was queried using international classification of disease (ICD-10) diagnostic codes to identify patients with primary diagnosis of NAFLD and secondary diagnosis of AMI. Basic demographic variables were analyzed to determine the disparities in prevalence of AMI among NAFLD patients. Univariate logistic regression model was used to compare the odds of development of AMI among NAFLD patients using demographic characteristics. Multivariate logistic regression analysis was done to determine whether NAFLD is an independent predictor of AMI. Results: A total of 58,519 patients had a diagnosis of NAFLD and of these, 5,448 had AMI. Of these, 61% were males, 82% were aged 50 years and over, 68% were white, 8% Black, 16% Hispanic, Asian or Pacific Islander. Females were less likely to have AMI [OR 0.46, 95% CI 0.43-0.48]. Patients &lt;50 years with NAFLD were less likely to develop AMI [OR 0.41, 95% CI 0.38-0.44]. Compared to the whites, blacks [OR 0.57, 95% CI 0.51-0.61, p&lt; 0.001] were less likely to have AMI. However, Hispanics [OR 1.16, 95% CI 1.07-1.25, p&lt; 0.001] and Asian and Pacific Islanders [OR 1.31, 95% CI 1.13-1.51, p&lt; 0.001] were more likely to have AMI compared to the whites. On multivariate analysis, NAFLD was found to be an independent predictor of AMI [OR 1.55, 95% CI 1.51-1.60, p&lt; 0.001] after controlling for sociodemographic variables such as age, sex, race, smoking status, insurance status, hospital location and teaching status, and clinical variables such as previous MI, Congestive heart failure, diabetes mellitus, chronic kidney disease, hyperlipidemia, and hypertension. Conclusions: This analysis suggests older white males with NAFLD had a higher prevalence of AMI and that NAFLD is an independent predictor of AMI.